Research Summary

Michelle’s lab develops innovative approaches to screen for chemical tools and drug leads, using biophysical approaches like fragment-based drug discovery and biological approaches including high-content imaging with primary cells and organisms. Our goal is to demonstrate ‘druggability’ of new target classes and to use our compounds to discover new targets for drug discovery. Areas of interest include protein-protein interactions, allosteric and scaffolding sites in enzymes, and orphan and neglected diseases. Michelle is co-Director of the Small Molecule Discovery Center, a collaborative research and core lab that includes a high-throughput screening facility and medicinal chemistry (smdc.ucsf.edu).

Research Funding

  • January 1, 2023 - November 30, 2027 - Development of caspase-6 inhibitors for treatment of NASH , Co-Investigator . Sponsor: NIH, Sponsor Award ID: R01DK135289
  • September 15, 2022 - August 31, 2026 - Systematic stabilization of specific protein-protein interactions , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01GM147696
  • September 30, 2023 - February 28, 2025 - Optimizing brain penetrance of caspase-6 inhibitors to treat neurodegenerative diseases , Co-Investigator . Sponsor: NIH, Sponsor Award ID: R41AG078036
  • July 1, 2020 - June 30, 2024 - Discovery of Small Molecule Ligands for PHD1 Reader Domain of Histone Demethylase KDM5A , Co-Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01CA250459
  • September 5, 2018 - July 31, 2022 - Protein and small-molecule tools to probe the conformational dependence of the VCP/p97 protein-protein interaction network , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01GM130145
  • June 1, 2021 - May 31, 2022 - Bruker Sierra SPR-24 Pro , Principal Investigator . Sponsor: NIH, Sponsor Award ID: S10OD030265
  • March 23, 2016 - February 29, 2020 - A high content screen dissecting ciliogenesis and oncogenic Hedgehog signaling , Co-Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01CA181231
  • September 30, 2013 - February 28, 2019 - Translational Studies Linking Aging and Cancer , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01AG044515
  • July 1, 2014 - April 30, 2017 - Screening for inhibitors of p300-mediated tau acetylation for Alzheimer's Disease , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R21AG046526
  • June 5, 2013 - May 31, 2016 - Exploring statins as a small molecule therapy for treatment of schistosomiasis , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R21AI107390
  • May 15, 2010 - April 30, 2015 - An automated high throughput phenotypic screen for schistosomiasis drug discovery , Co-Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01AI089896
  • September 27, 2010 - August 31, 2012 - A novel high content screen for regulators of ciliogenesis and Hedgehog signaling , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R21NS066448
  • January 1, 2008 - December 31, 2008 - 2008 Biomolecular Interactions and Methods Gordon Research Conference , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R13GM083379

Education

1990, Bryn Mawr College, Bryn Mawr, PA, B.A., Chemistry
1997, California Institute of Technology, Pasadena, CA, Ph.D., Chemistry
1999, Genentech, Inc, South San Francisco, CA and Sunesis Pharmaceuticals, Redwood City, CA, Postdoctoral fellowship, Protein Engineering

Honors & Awards

  • 1990    
    European Traveling Fellowship    Bryn Mawr College
  • 1991    
    Blodgett Fellowship    General Electric Foundation
  • 1992    
    Predoctoral Fellowship    National Science Foundation
  • 1995    
    Traineeship    National Institutes of Health
  • 1997    
    Postdoctoral Fellowship    Damon Runyon Cancer Research Foundation 
  • 2014    
    Finalist    SLAS Innovation Award
  • 2018    
    Breakthrough Chemical Biology Awardee    Ono Pharma Foundation     
  • 2018    
    Webster-Sibilsky Keynote Lecture    University of Illinois, Chicago    
  • 2019    
    Briggs Lecture    University of Texas Health San Antonio    
  • 2021    
    Fellow    Society for Laboratory Automation and Screening    
  • 2024    
    Cope Scholar    American Chemical Society, Organic Division    
  • 2024    
    Gordon Hammes Lectureship    American Chemical Society, Biochemisty    

Selected Publications

  1. Chou J, Robinson TM, Egusa EA, Lodha R, Zhang M, Badura M, Mikayelyan M, Delavan HM, Swinderman J, Wilson C, Zhu J, Das R, Nguyen M, Loehr A, Golsorkhi T, Simmons A, Abida W, Chinnaiyan AM, Arkin MR, Small EJ, Quigley DA, Yang L, Kim M, Ashworth A, Feng FY. Synthetic Lethal Targeting of CDK12-Deficient Prostate Cancer with PARP Inhibitors. Clin Cancer Res. 2024 Dec 02; 30(23):5445-5458.  View on PubMed
  2. Liara Rizzi, Julio C. Rojas, Andrew J. Ambrose, Marcio Luiz Figueredo Balthazar, Michelle R. Arkin, Lea T. Grinberg. D13 caspase-6-cleaved tau, a new biomarker to complement Alzheimer’s disease diagnosis. Alzheimer's & Dementia. 2024 Dec 1; 20(Suppl 8):e095421.  View on PubMed
  3. Ian Michael Oh, Song Hua Li, Felipe Luiz Pereira, Prabhleen Kaur, Anya Raju, Rushil Jerfy, Claudia Kimie Suemoto, Renata Elaine Paraizo Leite, Vitor Ribeiro Paes, Roberta Diehl Rodriguez, Andrew J. Ambrose, Salvatore Spina, William W. Seeley, Bruce L. Miller, Michelle R. Arkin, Lea T. Grinberg. Truncated tau accumulates before hyperphosphorylated tau and in relatively distinct neuronal subpopulations in entorhinal cortex and inferior temporal gyrus in Alzheimer’s disease patients. Alzheimer's & Dementia. 2024 Dec 1; 20(Suppl 1):e093137.  View on PubMed
  4. Gendelev L, Taylor J, Myers-Turnbull D, Chen S, McCarroll MN, Arkin MR, Kokel D, Keiser MJ. Deep phenotypic profiling of neuroactive drugs in larval zebrafish. Nat Commun. 2024 Nov 17; 15(1):9955.  View on PubMed
  5. Theofilas P, Wang C, Butler D, Morales DO, Petersen C, Ambrose A, Chin B, Yang T, Khan S, Ng R, Kayed R, Karch CM, Miller BL, Gestwicki JE, Gan L, Temple S, Arkin MR, Grinberg LT. iPSC-induced neurons with the V337M MAPT mutation are selectively vulnerable to caspase-mediated cleavage of tau and apoptotic cell death. Mol Cell Neurosci. 2024 Sep; 130:103954.  View on PubMed
  6. Somsen BA, Cossar PJ, Arkin MR, Brunsveld L, Ottmann C. 14-3-3 Protein-Protein Interactions: From Mechanistic Understanding to Their Small-Molecule Stabilization. Chembiochem. 2024 Jul 15; 25(14):e202400214.  View on PubMed
  7. Vickery HR, Virta JM, Konstantinidou M, Arkin MR. Development of a NanoBRET assay for evaluation of 14-3-3σ molecular glues. SLAS Discov. 2024 Jul; 29(5):100165.  View on PubMed
  8. Silva DB, Trinidad M, Ljungdahl A, Revalde JL, Berguig GY, Wallace W, Patrick CS, Bomba L, Arkin M, Dong S, Estrada K, Hutchinson K, LeBowitz JH, Schlessinger A, Johannesen KM, Møller RS, Giacomini KM, Froelich S, Sanders SJ, Wuster A. Haploinsufficiency underlies the neurodevelopmental consequences of SLC6A1 variants. Am J Hum Genet. 2024 06 06; 111(6):1222-1238.  View on PubMed
  9. Konstantinidou M, Arkin MR. Molecular glues for protein-protein interactions: Progressing toward a new dream. Cell Chem Biol. 2024 Jun 20; 31(6):1064-1088.  View on PubMed
  10. D'Ippolito RA, Rabara D, Blanco MA, Alberico E, Drew MR, Ramakrishnan N, Sontan D, Widmeyer SRT, Scheidemantle GM, Messing S, Turner D, Arkin M, Maciag AE, Stephen AG, Esposito D, McCormick F, Nissley DV, DeHart CJ. A Top-Down Proteomic Assay to Evaluate KRAS4B-Compound Engagement. Anal Chem. 2024 04 02; 96(13):5223-5231.  View on PubMed
  11. Lee JY, Reyes NS, Ravishankar S, Zhou M, Krasilnikov M, Ringler C, Pohan G, Wilson C, Ang KK, Wolters PJ, Tsukui T, Sheppard D, Arkin MR, Peng T. An in vivo screening platform identifies senolytic compounds that target p16INK4a+ fibroblasts in lung fibrosis. J Clin Invest. 2024 Mar 07; 134(9).  View on PubMed
  12. Jiang Z, Kuo YH, Arkin MR. Synthetic autophagy receptor. Autophagy. 2024 03; 20(3):701-703.  View on PubMed
  13. Ortiz G, Longbotham JE, Qin SL, Zhang MY, Lee GM, Neitz RJ, Kelly MJS, Arkin MR, Fujimori DG. Identifying ligands for the PHD1 finger of KDM5A through high-throughput screening. RSC Chem Biol. 2024 Mar 06; 5(3):209-215.  View on PubMed
  14. Braxton JR, Altobelli CR, Tucker MR, Tse E, Thwin AC, Arkin MR, Southworth DR. The p97/VCP adaptor UBXD1 drives AAA+ remodeling and ring opening through multi-domain tethered interactions. Nat Struct Mol Biol. 2023 Dec; 30(12):2009-2019.  View on PubMed
  15. Jiang Z, Kuo YH, Arkin MR. Autophagy Receptor-Inspired Antibody-Fusion Proteins for Targeted Intracellular Degradation. J Am Chem Soc. 2023 11 08; 145(44):23939-23947.  View on PubMed
  16. Konstantinidou M, Visser EJ, Vandenboorn E, Chen S, Jaishankar P, Overmans M, Dutta S, Neitz RJ, Renslo AR, Ottmann C, Brunsveld L, Arkin MR. Structure-Based Optimization of Covalent, Small-Molecule Stabilizers of the 14-3-3σ/ERα Protein-Protein Interaction from Nonselective Fragments. J Am Chem Soc. 2023 09 20; 145(37):20328-20343.  View on PubMed
  17. Visser EJ, Jaishankar P, Sijbesma E, Pennings MAM, Vandenboorn EMF, Guillory X, Neitz RJ, Morrow J, Dutta S, Renslo AR, Brunsveld L, Arkin MR, Ottmann C. From Tethered to Freestanding Stabilizers of 14-3-3 Protein-Protein Interactions through Fragment Linking. Angew Chem Int Ed Engl. 2023 09 11; 62(37):e202308004.  View on PubMed
  18. Emira J. Visser, Priyadarshini Jaishankar, Eline Sijbesma, Marloes A.M. Pennings, Edmee M.F. Vandenboorn, Xavier Guillory, R. Jeffrey Neitz, John Morrow, Shubhankar Dutta, Adam R. Renslo, Luc Brunsveld, Michelle R. Arkin, Christian Ottmann. From tethered to freestanding stabilizers of 14-3-3 protein-protein interactions via fragment linking. Angewandte Chemie. 2023 Aug 1.  View on PubMed
  19. Togo T, Tram L, Denton LG, ElHilali-Pollard X, Gu J, Jiang J, Liu C, Zhao Y, Zhao Y, Zheng Y, Zheng Y, Yang J, Fan P, Arkin MR, Härmä H, Sun D, Canan SS, Wheeler SE, Renslo AR. Systematic Study of Heteroarene Stacking Using a Congeneric Set of Molecular Glues for Procaspase-6. J Med Chem. 2023 07 27; 66(14):9784-9796.  View on PubMed
  20. Braxton JR, Altobelli CR, Tucker MR, Tse E, Thwin AC, Arkin MR, Southworth DR. The p97/VCP adapter UBXD1 drives AAA+ remodeling and ring opening through multi-domain tethered interactions. bioRxiv. 2023 May 15.  View on PubMed

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